Larsen and Lish (Larsen, A. A. and Lish, P. M. (1964) Nature, 203, 1283-1284) reported the biological activity of a series of phenethanolamine bearing alkyl sulfonamido groups on the benzene ring. Within this series, some compounds possessed adrenergic and anti-adrenergic actions including alpha-adrenergic receptor block or receptor stimulation, beta-adrenergic receptor block or receptor stimulation. D-(+) sotalol is a beta-blocker (Uloth, R. H., Kirk, J. R., Gould, W. A., and Larsen, A. A. (1966) Sulfonanilides, 9, 88-96). Unlike other beta-blockers, it has class III antiarrhythmic properties (Lish, P. A., Weikel, J. H., and Dungan, K. W. (1965) J. Pharma. and Exper. Therapeutics, 149, 161-173). The beta-adrenergic blocking drugs such as propanolol and sotalol have been separated chemically into the dextro and levo rotatory optical isomers, and it has been demonstrated that the activity of the D(+) isomer is 50 times that of the corresponding L(-) isomer (Somani, P., and Bachand, T. (1969) Eur. J. Pharma, 7, 239-247). Thus, it would be highly desirable to have a facile stereoselective process for obtaining the enantiomeric pure isomers of the above described sulfonamido compounds.
The use of enzymes and microorganisms to produce certain optically active compounds is known in the art (see, for example, U.S. Pat. No. 5,106,736; U.S. Pat. No. 4,857,468; Akita, H. et al., (1984) Chem. Pharm. Bull., 32(4), 1342-1348; Hummel, W. (1990) Biotechnology Letters, 12(60), 403-408; and Schneider, M. P. et al., pp 483-529 in Bioflavour '87, P. Schreier, editor, De Grugter, Berlin (1988)). However, heretofore the stereoselective microbial/enzymatic reduction of certain keto group-containing compounds as hereinafter described has been unknown.
We have discovered the stereoselective microbial reduction of certain ketones such as N-(4-(2-chloroacetyl)phenyl)-methanesulfomamide to the corresponding (+)-alkanols. The alkanols are either biologically active themselves or are key chiral intermediates for the synthesis of certain cardiovascular drugs such as D-(+) sotalol.